Influence of preoperative dexamethasone therapy on proliferating cell nuclear antigen (PCNA) expression in comparison to other parameters in meningiomas.

We conducted a trial in 42 benign and malignant meningiomas to assess a possible influence of preoperative dexamethasone therapy on mitotic index, labelling indices of proliferating cell nuclear antigen (PCNA), progesterone receptor, epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, cathepsin D, gamma-gamma enolase as well as the mean number of silver-stained nucleolar organizer region-associated proteins (AgNORs). Tumors with preceding dexamethasone therapy for more than 1 day display significantly less immunohistochemical staining for PCNA. A correlation between the labelling index of PCNA and the degree of malignancy could not be identified. There was no significant effect of preoperative dexamethasone therapy on the other parameters. Our data suggest that dexamethasone may selectively inhibit the expression of PCNA in the G1/S-phase of the cell cycle. Thus, we emphasize the necessity to heed factors, e.g. dexamethasone, which may affect the expression of proliferating markers.

Unusual choristoma of the parotid gland in a girl. A possible trichoadenoma.

An 8-year-old girl had a painless circumscribed nodule in the right parotid gland for 4 weeks. A tumour (1.3 cm diameter) within the salivary gland parenchyma showed small cystic spaces with horn-like material macroscopically. The tumour tissue contained solid squamous cell formations and cystic spaces limited by multilayered squamous epithelium and covered by layers of ortho- and parakeratotic cells. The cystic spaces contained keratotic lamellae. In some areas pin-like epithelial proliferations were seen. All epithelial cells were characterized by uniform nuclei, and no atypical mitoses were seen. Keratinizated masses with partial calcification were occasionally located in the interstitial tissue and replaced by multinucleated giant cells. The tumour was classified as a choristoma and resembled a trichoadenoma. The ectodermally derived oral and salivary gland epithelium may be the source of skin-like or adnexal tumours.

Acute and long-term efficacy of antituberculous treatment in HIV-seropositive patients with tuberculosis: a study of 36 cases.

Thirty-six consecutively observed HIV-seropositive patients with tuberculosis, including 31 patients with AIDS, who received antituberculous treatment, were followed up to evaluate its efficacy. Treatment with standard antituberculous regimens was intended except when an individual's condition required a modified therapeutic approach. Therapeutic failure occurred in five patients (14%) while on treatment, one also had a post-treatment relapse. Treatment failure was associated with drug resistance and non-compliance in three patients and in another two, both of whom died early in the course of their disease, with HIV-related conditions other than tuberculosis. The median relapse-free post-treatment follow-up time in 24 patients in whom treatment did not fail was 13 months (range 4-67). Standard antituberculous treatment is highly effective in the immediate and long-term treatment of HIV-related tuberculosis provided that drug susceptibility and treatment compliance are confirmed.

Simultaneous production of the alpha-subunit of glycoprotein hormones and other hormones in pituitary adenomas.

The immunohistological classification of 97 pituitary adenomas revealed in 34 cases alpha-subunit (a-su) positive cells in the tumor tissue. In 15 cases a-su was the only hormone found, in 11 cases the beta-subunits of the glycoprotein hormones could also be detected (10 cases with LH/FSH and 1 case with TSH). In 8 cases a-su was found simultaneously together with other hormones of the pituitary (ACTH and a-su in 1 case, GH and a-su in 4 cases, prolactin and a-su in 2 cases, prolactin, GH and a-su in 1 case). A-su could be demonstrated to be partly simultaneously produced together with these hormones in identical cells and secretory granules. Next to prolactin, the a-su was the second most frequently occurring hormone that could be detected immunohistologically in our material.

Epithelial and melanoma antigens in gliosarcoma. An immunohistochemical study.

Gliosarcomas are mixed tumors with malignant glial and mesenchymal elements. The number of GFAP-positive tumor cells decreases with the increase of sarcomatous components, until whole areas may be GFAP negative. These distinct differentiations may, however, lead to false interpretations in small tissue samples. In this connection, it is of interest that, according to other reports, glial tumors may be positive for different anti-keratin antibodies and this prompted us to undertake a systematic investigation of the immunoreactivity of gliosarcomas using a panel of well-characterized monoclonal antibodies against cytokeratins (KL1, AE 1/3, Lu-5, CK-19, CK MNF 116 and Ma-903). These cases were further studied with the anti-epithelial non-cytokeratin antibodies EMA, HEA 125, Ber-EP4, CEA as well as the melanoma-antibody HMB-45, Leu-M1, GFAP and vimentin. As screening study we examined 20 cerebral metastatic carcinomas, 21 malignant gliomas (including 6 gliosarcomas) and 3 metastatic melanomas with the monoclonal antibodies KL1 and HMB-45. All cerebral metastatic carcinomas and 4/6 gliosarcomas were positive for KL1, whereas all melanomas, 2 metastatic carcinomas and 3 gliosarcomas showed an immunostaining with HMB-45. All gliosarcomas were positive with at least one of the tested anti-cytokeratin antibodies. The gliosarcomas did not show an immunoreaction in any of the cases when CEA, HEA 125, Ber-EP4, EMA or Leu M1 were applied. In our opinion, the monoclonal antibodies HEA 125 and Ber-EP4 could obviously be helpful in differentiating gliosarcomas from metastatic carcinomas.

Immunohistological detection of estrogen and progesterone receptors in multiple and well differentiated leiomyomatous lung tumors in women with uterine leiomyomas (so-called benign metastasizing leiomyomas). A report on 5 cases.

Seventy-four cases of so-called "benign metastasizing uterine leiomyomata" are reported in the literature. In these cases, well differentiated, leiomyomatous lung tumors developed, usually after a period of several years. Histologically, these tumors appear to be benign. We report on five more such cases in which we investigated the contents of estrogen and progesterone receptors in the pulmonary tumors by immunohistological procedures. All the lung tumors exhibited a high content of progesterone receptors, and in 4 out of the 5 cases a high estrogen receptor content was also found. Modern immunohistological techniques permit the investigation of routinely fixed tissue blocks, and it is thus recommended that the contents of these hormone receptors should be determined in well differentiated, leiomyomatous lung tumors from women. This would both provide information on the pathogenesis of these tumors and establish a basis for possible later institution of hormone treatment. It is likely that the majority of these lung tumors are in fact metastases of extremely well differentiated leiomyosarcomas of the uterus. The possibility that lung tumors of this type may constitute a small group that develop in situ as hormone-sensitive proliferations cannot, however, be fully excluded.

Proliferating cell nuclear antigen (PCNA) in atypical and malignant meningiomas.

Because it is not easy to determine the tumor status of meningiomas by current diagnostic procedures, we investigated these tumors immunohistochemically using the monoclonal antibody PC 10. This antibody recognizes a fixation- and processing-resistant epitope of the proliferating cell nuclear antigen (PCNA), which is a 36-KD nuclear antigen associated with the cell cycle. We studied paraffin-embedded and formalin-fixed tissue specimens of a group of 21 atypical/malignant meningiomas together with 18 benign meningiomas. PCNA staining results were compared with the mean number of silver-stained nucleolar organizer region-associated proteins (AgNORs), tumor grading, and mitotic indices of these tumors. The percentage of PCNA-positive cells was found to range between 0.1% and 40%, irrespective of the tumor grade. When all tumors were collectively considered, no positive correlation was found between PCNA scores and histologic grading and only a weak one between PCNA score and mitotic index. A higher correlation was seen between AgNOR counts and tumor grading. Our results suggest that PCNA labeling and histologic grading seem to be independent parameters. The correlations found between AgNOR counts and tumor grading should be substantiated in further series.

Extracerebral toxoplasmosis in AIDS. Histological and immunohistological findings based on 80 autopsy cases.

Despite the great amount of literature concerning toxoplasmic encephalitis in AIDS patients, little is known about extracerebral toxoplasmosis. Therefore we conducted a study of 80 autopsy cases to estimate the frequency of extracerebral toxoplasmosis. A control group of 50 cases was completely negative for all markers applied. In 35 of the 80 AIDS-cases (43.7%), organisms could be detected. In 13 cases (16.2%) there was an extracerebral toxoplasmosis; 4 cases (5%) showed only extracerebral involvement and in 9 cases (11.2%), extracerebral toxoplasmosis occurred in combination with cerebral manifestations. In 22 cases (27.5%), only cerebral toxoplasmosis was found. The following organs were involved: cardiac muscle (15%), lungs (6.2%), liver (5%), pancreas (5%), gastrointestinal tract (6.2%), adrenal glands (5%), lymph nodes (5%) and testis (3.7%). In individual cases further organs, not mentioned above, were involved. Pseudocysts could be demonstrated within necroses and inflammatory foci by conventional staining, whereas trophozoites became apparent only immunohistologically.

HEA 125 and Ber EP4: two monoclonal anti-epithelial, non-cytokeratin antibodies distinguishing metastatic carcinomas from glial tumors.

Since some monoclonal anti-cytokeratin antibodies also react with glial tumors to a relatively high degree, an immunohistochemical study was performed to examine the reaction of 40 glial tumors and neuroepithelial tumors with glial differentiation to the monoclonal anti-epithelial non-cytokeratin antibodies HEA 125 and Ber EP4. Seven of these tumors were cytokeratin-positive neoplasms (6 gliosarcomas and 1 ependymoma). In addition, 20 metastatic carcinomas were investigated. All glial tumors showed a negative reaction to HEA 125 and Ber EP4, whereas 19 of the 20 metastatic carcinomas were positive with these two monoclonal antibodies. HEA 125 and Ber EP4 thus can be used as additional markers especially in cytokeratin-negative small cell carcinomas.

Cerebral lymphoma in AIDS. Clinical, radiological, neuropathological and immunopathological study.

Neuropathological findings from 8 individual cases of cerebral lymphomas in AIDS patients with consideration of the clinical, radiological, immunopathological, and other pertinent data selected from a series of 80 patients between 1985 and 1989 were studied. A wide variation in pathology was noted among our cases. It has been shown that lymphoma as a neuropathological diagnosis can coexist with a wide range of other characteristics, including toxoplasmosis, glial nodules, neuronophagia, degeneration, bleeding, hypoxia, progressive multifocal leucoencephalopathy, and myelopathy, although none of these attributes appeared more than casually interrelated. In general, the late-stage manifestations of lymphoma as were observed in this study, tended to be poorly localized, often simultaneously meningeal, perivascular, and diffuse in character. An important distinction between cerebral lymphomas of AIDS and non-AIDS patients is the highly atypical, clinically unreliable computer tomographic signals observed in several of our cases. Five of the six immunopathological investigations showed a preponderance of B-cell markers, corresponding in toto to high-grade non-Hodgkin lymphoma. One case exhibited immunohistological markers typical of Hodgkin's lymphoma (antibody CD-30). Of 6 obtainable serum specimens from our 8 cases, 4 showed high (greater than 2000) IgG titers against the EBNA-1 antigen of Epstein-Barr virus (EBV), of these three had IgM titers further supporting viral reactivation. One showed a normal IgG titer, yet with a significantly raised IgM titer.

Immunohistochemical demonstration of carcinoembryonic antigen (CEA) and its correlation with grading and staging on tissue sections of urinary bladder carcinomas.

In 150 transitional cell carcinomas (TCC) of the urinary bladder, 50 each of Grades 1, 2, and 3, the content of carcinoembryonic antigen (CEA) was examined immunocytochemically and correlated to grading and staging. Fifty-seven percent of the TCC contained CEA-positive tumor cells. Their distribution in tumor tissue is described. They were found in 24% of Grade 1 cases, in 72% of Grade 2 carcinomas, and in 76% of Grade 3 tumors. None of the Grade 1 cases contained more than 10% CEA-positive cells, whereas 34% and 40% of the Grade 2 and 3 tumors, respectively, revealed more than 10% CEA-positive tumor cells. According to the correlation found between grading and staging, the percentage of TCC containing CEA-positive tumor cells was 34% in pTA, 59% in pT1, and 80% in pT2/3 tumors. The results show a correlation between CEA content of tumor tissue and histopathologic malignancy in TCC of urinary bladder.

[Microcarcinoidosis of the stomach. Diffuse hyperplasia of endocrine c ells and multiple polyp-like carcinoids]. / Mikrokarzinoidose des Magens. Diffuse Hyperplasie endokriner Zellen und multiple polypöse Karzinoide.

A diffuse peptide microcarcinoidosis was observed both in a 56-year-old man with chronic atrophic gastritis and in a 33-year-old female with chronic atrophic gastritis and pernicious anaemia. Besides hyperplasia of endocrine cells at the base of gastric fundus and corpus mucosa with infiltration of the mucosal muscular layer multiple macro- and micropolyp carcinoids were present. In both cases serotonin was demonstrated immunohistochemically in the intestinal metaplastic mucosal changes, in the microcarcinoidosis foci and in the carcinoids. However, no appropriate clinical symptomatology was observed. The diagnosis can already be made by biopsy which must be deep enough and include gastric mucosa containing the mucosal muscular layer. Should gastric carcinoid be established histologically the other macroscopically normal mucosa must also be biopsied for exclusion of diffuse microcarcinoidosis as intermediate form of a multiple carcinoid. In such a case treatment consists of total gastrectomy.

[Changes of microenvironment and tumor cell heterogeneity--consequences for bioptic diagnosis]. / Anderung des Mikromilieus und Tumorzellheterogenität--Konsequenzen für die bioptische Diagnostik.

During the last several decades, immunohistochemical studies of tumors, along with other approaches, have suggested that the clinical and biological progression results, at least in part, from the sequential appearance within the neoplasm of cellular subpopulations whose new characteristics reflect specific somatic genetic changes. However, CNS may provide a different microenvironment for activation and proliferation than other tissues. The tissue-specific distribution of intermediate filament proteins, in particular the keratins, permits their use as marker in histopathology, but several important exceptions are recognized. In this connection, it is of interest that, according to the other reports, glial tumors may be positive for different anti-keratin antibodies. However, the gliomas did not show an immunoreaction in any of the cases when HEA-125 and Ber-EP4 were applied. The great number of multihormonal pituitary adenomas and possible change of the immunohistochemically detectable hormone status in cases of recurrent tumors have particularly re-emphasized the need for new thinking about patterns of classification. The diagnosis of malignant melanoma has been considerably facilitated recently by the introduction of immunohistological labelling with antibodies selective against melanoma antigen (HMB-45). Our results confirmed the necessity of cautious interpretation of HMB-45 immunoreactivity because a HMB-45 expression can be observed in several non-melanotic tumors.

[Middle ear adenoma. Long-term course of a rare neoplasm]. / Das Mittelohradenom. Langzeitverlauf einer seltenen Neoplasie.

Adenomas of the middle ear are rare benign glandular neoplasms arising from the middle ear mucosa. After previous operations 25 and 15 years before, a 67-year-old female complained about dizziness, tinnitus, and unilateral hearing loss on the left side. A tumor in the tympanum that was revealed by otoscopy could be removed completely. Histological examinations showed an adenoma of the middle ear with cholesteatoma. This was inconsistent with the histological result of the operation in 1983, which had described a hidradenoma. An exact analysis of the preparations confirmed that a middle ear adenoma had already been present in 1983. Hidradenoma is one of the most important differential diagnoses. The characteristic histological sign of middle ear adenomas in contrast to hidradenomas is the lack of myoepithelial cells. In addition, it is very difficult to differentiate middle ear adenoma and adenocarcinoma using histopathological and clinical methods. Therefore, thorough follow-up is mandatory for patients after surgical treatment of middle ear adenomas.

[Localized amyloidosis of the ENT area]. / Die lokalisierte Amyloidose im HNO-Bereich.

Although amyloidosis is in general a systemic disorder, it may occur as an isolated lesion, especially in the head and neck. The actual classification of amyloidosis is dependent on the biochemical nature of its protein deposits. In the present report, the symptoms and diagnosis of localized amyloidosis are discussed with special regard to histological findings.

[Epidermoid cyst of the testis]. / Epidermoidzyste des Hodens.

Epidermoid cysts of the testis are very rare tumours. It is reported on a case of a typical epidermoid cyst. Based on the histopathological facts, the problems of the diagnostic and therapeutic approach are discussed.

Vascular tumors in the region of the breast.

Three vascular tumors in the breast region with different degrees of differentiation are presented. The first neoplasm is a haemangiosarcoma (of the vascular neoplasms, these tumors are the type which occur most frequently in the breast). Haemangiosarcomas show an infiltrative growth of atypical blood capillaries, frequently with formation of highly cellular and solid capillary sprouts. Ultrastructurally, the tumor cells are characterized as endothelial, also in the region of the capillary sprouts. The second tumor (an angiosarcoma in Stewart-Treves-syndrome, STS) is characterized by an intensive endothelial proliferation. Solid spindle-celled regions are also found in which the tumor cells correspond to undifferentiated mesenchymal cells, but other cells possessing properties of smooth muscle cells and pericytes may be found. The third tumor corresponds light and electron microscopically to a haemangiopericytoma of the soft tissue. The pericytic character of the tumor cells is most clearly seen in the immediate vicinity of the vessels. With increasing distance from the capillaries, the tumor cells take on the characteristics of fibroblasts. The tumors reflect the diversity of the angioplastic differentiation potential of the mesenchyme.